Thanks Jonas! PdCO was great to work with ☺️

In conclusion, we found LC heterogeneity in the context of sleep and arousal. More specifically, our work reveals a specific pathway critical to sound evoked awakenings.

Finally, selective synaptic silencing using an optoGPCR, PdCO, demonstrated that silencing LC synapses in the PRN is sufficient in elevating sigma power in EEG during NREM sleep.

Optoactivation of LC neurons projecting to each of our target regions showed that the influence of LC fast activation on sound evoked awakenings depended both on the population identity (only the LC-PRN) and on the precise timing in synchronicity with sounds.

NE monitoring in these targets during sleep and while playing sounds revealed a unique fast NE surge in the PRN in response to sounds. Importantly, this fast surge determined whether the sounds would awaken the mice.

Comparing two LC pathways- to the basal forebrain and to the brainstem PRN, we found that LC neurons projecting to the two regions were partially distinct anatomically.